A knockout approach to identifying genes involved in epidermal development and homeostasis. These studies will identify new genes which play a role in the development or maintenance of the skin, some of which may subsequently be shown to play a role in disease. The project capitalises on an investment of tens of millions of dollars by the Wellcome Trust in generating a significant cohort of knockout mice. Our involvement in this international initiative will ensure Australia's participation in ....A knockout approach to identifying genes involved in epidermal development and homeostasis. These studies will identify new genes which play a role in the development or maintenance of the skin, some of which may subsequently be shown to play a role in disease. The project capitalises on an investment of tens of millions of dollars by the Wellcome Trust in generating a significant cohort of knockout mice. Our involvement in this international initiative will ensure Australia's participation in a project at the forefront of mouse genetics, using cutting edge infrastructure and technologies to provide insights into the complement of genes involved in skin biology. Models of interest will be repatriated to Australia for further study capitalising on existing infrastructure provided through the NCRIS funding program. Read moreRead less
Pathogen sensing in systemic inflammatory disease. The initiation, amplification and quenching of an immune response is a carefully orchestrated process that eliminates invading pathogens while minimising collateral damage to host tissues. This research focuses on proteins that restrict immune responses to prevent inflammatory diseases such as rheumatoid arthritis, psoriasis and inflammatory bowel disease. This work will also explore the role of a potassium channel that protects the host from or ....Pathogen sensing in systemic inflammatory disease. The initiation, amplification and quenching of an immune response is a carefully orchestrated process that eliminates invading pathogens while minimising collateral damage to host tissues. This research focuses on proteins that restrict immune responses to prevent inflammatory diseases such as rheumatoid arthritis, psoriasis and inflammatory bowel disease. This work will also explore the role of a potassium channel that protects the host from organ failure during an infection, by coupling the energy requirements of mounting an immune response, and organ function. This may have important implications for the management of sepsis, a systemic immune response associated with infection and the leading cause of death in critically ill patients.Read moreRead less
Shaping the heart in early development - new insights into cellular modelling processes. Heart health is an important contributor to quality of life and longevity. This research will provide new insights into the way hormonal influences early in development shape a healthy heart. The project builds on the application of recently patented, sophisticated cell imaging techniques. Research students and trainees recruited to this project will benefit from their involvement with this leading edge tech ....Shaping the heart in early development - new insights into cellular modelling processes. Heart health is an important contributor to quality of life and longevity. This research will provide new insights into the way hormonal influences early in development shape a healthy heart. The project builds on the application of recently patented, sophisticated cell imaging techniques. Research students and trainees recruited to this project will benefit from their involvement with this leading edge technology. These studies are important in providing a basis for developing optimal management strategies for congenital heart conditions and preterm infants. Improved knowledge of the cardiac effects of fetal and neonatal exposure to steroids (to assist with lung maturation in prematurity or to control maternal asthma) will be gained.Read moreRead less
Measurement and Prediction of Vulnerable Plaque Formation and Rupture. The major health problem of atherosclerosis, leading to large numbers of deaths from heart attacks and strokes worldwide, will be studied by a multidisciplinary team. Better understanding of how the disease evolves and its earlier detection will arise from this project, which will use synchrotron imaging and supercomputer prediction.
Novel sources of nitric oxide (NO) in cells: Implications for an endocrine role for NO. Communication between cells is essential for coordinating and controlling a healthy body. A key regulator and cell-communicating molecule is the gas, nitric oxide. Although nitric oxide is a simple substance we still do not fully understand all aspects of its cellular functions. It is assumed that nitric oxide is synthesised in the body and, after release, is rapidly metabolized and eliminated. Reductions in ....Novel sources of nitric oxide (NO) in cells: Implications for an endocrine role for NO. Communication between cells is essential for coordinating and controlling a healthy body. A key regulator and cell-communicating molecule is the gas, nitric oxide. Although nitric oxide is a simple substance we still do not fully understand all aspects of its cellular functions. It is assumed that nitric oxide is synthesised in the body and, after release, is rapidly metabolized and eliminated. Reductions in the levels of nitric oxide in the body are associated with several diseases states and states of dysfunction including cardiovascular disease, diabetes and also impotence. Professor Triggle's study seeks to characterize how tissues may store nitric oxide, thus prolonging the life of nitric oxide, and how such stores are released. Read moreRead less
Brain sodium channel: functional role of developmentally regulated alternative splicing. This project will identify the roles of neonatal and adult forms of a sodium channel in the function of neurons in the developing brain. Sodium channels are vital for brain function and this study will improve our understanding of the function of healthy brain as well as of underlying mechanisms of some neurological disorders.
The dynamics of viral latency in chronic infection. Although many acute infections can now be controlled, we still suffer from a large number of chronic infections such as HIV or herpes that cannot be eradicated. Many of these infections persist because they can lie dormant in a 'latent' state. How this latent state is established, and how long it lasts are important to understand if we want to control these infections. We have assembled a team of mathematicians, immunologists and virologists in ....The dynamics of viral latency in chronic infection. Although many acute infections can now be controlled, we still suffer from a large number of chronic infections such as HIV or herpes that cannot be eradicated. Many of these infections persist because they can lie dormant in a 'latent' state. How this latent state is established, and how long it lasts are important to understand if we want to control these infections. We have assembled a team of mathematicians, immunologists and virologists in order to study latent infection at the cellular level, and within infected monkeys. This will provide the first insights into the dynamics of latency - how these cells are produced and die - and should lead to novel approaches to controlling chronic infection.Read moreRead less
The role of palmitoylation in hair follicle and epidermal stem cell biology. A proteins activity can be shaped by sugar, phosphate and lipid modifications. This proposal will investigate the effects of the lipid modification called palmitoylation, about which we know very little. Our preliminary experiments suggest that palmitoylation is crucial for normal skin biology. We will explore its effects on the biology of the proteins which are modified, the cells in which they are found and the tis ....The role of palmitoylation in hair follicle and epidermal stem cell biology. A proteins activity can be shaped by sugar, phosphate and lipid modifications. This proposal will investigate the effects of the lipid modification called palmitoylation, about which we know very little. Our preliminary experiments suggest that palmitoylation is crucial for normal skin biology. We will explore its effects on the biology of the proteins which are modified, the cells in which they are found and the tissues in which they reside. Understanding more about these modifications will help us to learn more about the biology of our skin and will help us to understand diseases which affect our largest organ.Read moreRead less
Elucidating the post-transcriptional regulation of mast cell proteases. Mast cells (MCs) are immune cells that protect against pathogens but may induce deleterious inflammation. MC function is mediated by specific proteases that are pre-formed and stored in granules. These proteases have unique yet poorly understood mechanisms of regulation. The aim of the project is to use a novel suite of molecular tools and genetically modified mice to identify the critical regions of transcripts that post-tr ....Elucidating the post-transcriptional regulation of mast cell proteases. Mast cells (MCs) are immune cells that protect against pathogens but may induce deleterious inflammation. MC function is mediated by specific proteases that are pre-formed and stored in granules. These proteases have unique yet poorly understood mechanisms of regulation. The aim of the project is to use a novel suite of molecular tools and genetically modified mice to identify the critical regions of transcripts that post-transcriptionally regulate the production and storage of these proteins. The project aims to identify the RNA binding proteins, microRNAs and other novel factors that also regulate them. This is expected to elucidate the post-transcriptional mechanisms of regulation of MC proteases.Read moreRead less
In-vivo detection of airway injury and disease using phase contrast X-ray velocimetry. Currently diagnosis of lung disease, a major cause of death in humans, is based on clinical symptoms that do not usually manifest until the disease is well advanced. This project will develop a novel imaging technique, X-ray velocimetry, to detect changes in tissue before symptoms arise, potentially leading to strategies for managing lung diseases.